S222: EPCORITAMAB WITH RITUXIMAB + LENALIDOMIDE (R2) PROVIDES DURABLE RESPONSES IN PATIENTS WITH HIGH-RISK FOLLICULAR LYMPHOMA, REGARDLESS OF POD24 STATUS
Authors: Anna Sureda, Lorenzo Falchi, Sirpa Leppa, Joost Vermaat, Harald Holte, Martin Hutchings, Pieternella Lugtenburg, Sven de Vos, Pau Abrisqueta, Marcel Nijland, Reid W. Merryman, Jacob Haaber Christensen, Bjorn Wahlin, Kim Linton, Liwei Wang, Aqeel Abbas, Ali Rana, Syed Quadri, David Belada
Journal: HemaSphere (2023)

Background: Follicular lymphoma (FL) is a heterogeneous disease. Early progression after initial treatment with chemoimmunotherapy, or POD24, occurs in approximately 20% of patients and is a strong predictor of poor outcomes. There is no standard treatment approach for patients with high-risk, relapsed or refractory (R/R) FL, including those with disease that is primary refractory, double refractory, or refractory to prior anti-CD20 treatment and those with POD24. In these patients with a high unmet need, novel options are needed to improve efficacy. Epcoritamab, a subcutaneous T-cell–engaging bispecific antibody, demonstrated impressive single-agent antitumor activity and a manageable safety profile in R/R FL (Hutchings et al, Lancet 2021) and shows promise combined with standards of care. Aims: To present pooled analyses from cohorts 2a and 2b of the ongoing phase 1/2 EPCORE™ NHL-2 trial (NCT04663347) of epcoritamab + R2 in R/R FL. Methods: Patients with R/R CD20+ FL received subcutaneous epcoritamab + R2 for 12 cycles (28 d each). Epcoritamab was dosed QW in cycles 1–3, Q2W in cycles 4–9, and Q4W in cycles ≥10 (2a) or QW in cycles 1–2 and Q4W in cycles ≥3 (2b) for ≤2 y. Informed consent was obtained. Results: As of October 31, 2022, 109 R/R FL patients had received epcoritamab 48 mg + R2 in 2a and 2b. Median age was 65 y, 56% of patients had FLIPI 3–5, 61% had stage IV disease, and 59% had only 1 prior line of treatment. Most had received alkylating agents (92%) or anthracyclines (62%); 2 had prior CAR T. At a median follow-up of 8.8 mo (range, 1.2–18.5), 82% were still on treatment. The most common treatment-emergent AEs were CRS and neutropenia (48% each), injection-site reactions (38%), and fatigue (33%). CRS events were mostly low grade (G; 46% G1–2, 2% G3) and mostly occurred following the first full dose (cycle 1, day 15); all resolved and none led to discontinuation. ICANS occurred in 2 patients (G1, G2) and resolved. In 101 efficacy-evaluable patients, overall response rate (ORR) was 97%, with complete metabolic response (CMR) in 86%. Median time to any response and CMR was 1.4 mo. Estimated 6-mo progression-free survival was 93%. Notably, patients achieved higher ORR/CMR rates with epcoritamab + R2 vs their immediate prior therapy (ORR, 97% vs 85%; CMR, 86% vs 60%; Figure). High ORR/CMR rates were consistent across high-risk subgroups: POD24 (progression within 2 y of first-line treatment with chemoimmunotherapy, n=38; Figure), 95%/82%; subset of POD24 patients that received epcoritamab in second line (n=20), 95%/90%; double refractory (refractory to anti-CD20 and an alkylating agent, n=39; Figure), 92%/79%; refractory to last line of therapy (no response or relapse within 6 mo after last line of therapy, n=40; Figure), 93%/80%; primary refractory (no response or relapse within 6 mo after first-line treatment, n=39), 97%/87%; refractory to prior anti-CD20 treatment (n=49), 94%/84%. Additional data with longer follow-up will be presented. Summary/Conclusion: Epcoritamab + R2 showed potent antitumor activity and a manageable safety profile in a large R/R FL population. Encouraging responses were seen in patients with high-risk disease, suggesting subcutaneous epcoritamab may abrogate negative effects of high-risk features. A separate POD24 cohort is planned, and epcoritamab + R2 is being studied in the phase 3 EPCORE FL-1 trial (NCT05409066).Keywords: Hematological malignancy, Bispecific, Follicular lymphoma